DESCRIPTION: The proposal addresses the problem of how platelet surface glycoprotein Ib-IX (the receptor for von Willebrand factor) signals to activate the platelet following GPIb-vWf interaction. Progress has been made recently by the PI in identifying and characterizing a protein (29kDa) that is associated with GPIb-IX. The protein has been identified as P29, a modifier of protein kinase C, also termed a x-form of 14-3-3 which has phospholipase A2 activity. The proposal sets out to characterize the interaction between 14-3-3 and GP Ib-IX and to characterize the functions of 14-3-3. Specifically, four aims are proposed: first, further characterize the interaction between GPIb-IX and 14-3-3, second, examine the functions of P29 and how it is modulated by ligand binding to GPIIb-IX, third, characterize and express the phosholipase activity of P29, fourth, characterize the structural basis of the interaction between GPIb-IX and P29.